MARINOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MARINOL (MARINOL).
Dronabinol is a cannabinoid receptor agonist at CB1 and CB2 receptors. It stimulates appetite and reduces nausea/vomiting via central CB1 receptor activation.
| Metabolism | Hepatic, primarily via CYP2C9 and CYP3A4; active metabolite (11-hydroxy-dronabinol). Undergoes extensive first-pass metabolism. |
| Excretion | Primarily fecal (65%) with biliary excretion; renal excretion of metabolites accounts for ~20% (mostly as glucuronide conjugates). Less than 5% of unchanged drug is excreted renally. |
| Half-life | Dronabinol terminal half-life is 25–36 hours in adults, with a prolonged elimination phase (25–36 h) due to enteric recirculation. Chronic users may exhibit a shorter half-life due to enzyme induction. |
| Protein binding | 97–99% bound to plasma proteins, primarily albumin and lipoproteins. |
| Volume of Distribution | Approximately 10 L/kg, indicating extensive tissue sequestration, especially in lipid-rich and highly perfused organs (e.g., brain, adipose tissue). |
| Bioavailability | Oral bioavailability is low and variable (~10–20%) due to extensive first-pass hepatic metabolism. |
| Onset of Action | Oral: 30–60 minutes; peak effect at 2–4 hours. |
| Duration of Action | Oral: Appetite stimulation persists for 4–6 hours; psychoactive effects may last 4–6 hours, but some effects (e.g., euphoria, dizziness) can persist up to 24 hours. |
Dronabinol (Marinol) 2.5 mg orally twice daily, titrated to 5–20 mg daily in divided doses; max 20 mg/day. For chemotherapy-induced nausea/vomiting: 5 mg/m² orally 1–3 hours before chemotherapy, then every 2–4 hours up to 6 doses/day. For anorexia: 2.5 mg orally twice daily (before lunch and dinner).
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment recommendations for renal impairment; use caution in severe impairment. GFR <15 mL/min: consider reduced dose and monitor for CNS effects. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce starting dose to 2.5 mg once daily, titrate cautiously. Child-Pugh C: avoid use or use with extreme caution; maximum 2.5 mg once daily. |
| Pediatric use | Chemotherapy-induced nausea/vomiting: 5 mg/m² orally 1–3 hours before chemotherapy, then every 2–4 hours up to 6 doses/day; maximum 15 mg/m² per dose. Not approved for anorexia in children. Doses adjusted for severe hepatic impairment. |
| Geriatric use | Initiate at 2.5 mg orally once daily; titrate slowly due to increased sensitivity to CNS effects (dizziness, confusion, sedation). Monitor for falls and cognitive impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MARINOL (MARINOL).
| Breastfeeding | Contraindicated in breastfeeding. Dronabinol is excreted into human milk; M/P ratio unknown. Potential for CNS effects and other adverse reactions in nursing infants. |
| Teratogenic Risk | Pregnancy Category C. First trimester: potential risk of teratogenicity based on animal studies; human data limited. Second/third trimesters: possible adverse effects on fetal brain development; avoid use unless potential benefit justifies risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to dronabinol or any component of the formulation.","Allergic reaction to sesame oil (capsule contains sesame oil).","Concurrent use with disulfiram (alcohol content in oral solution)."]
| Precautions | ["May cause psychological dependence; use with caution in patients with psychiatric disorders.","May impair cognitive function and motor skills; avoid driving or operating machinery.","Cardiovascular effects: tachycardia, hypertension, hypotension; use caution in patients with cardiac disease.","Seizures: may lower seizure threshold.","Central nervous system depression: additive effects with alcohol and other CNS depressants."] |
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| Monitor for maternal CNS depression, dizziness, hypotension. Fetal monitoring for growth and well-being if used beyond first trimester. Avoid use in pregnancy unless benefit outweighs risk. |
| Fertility Effects | Dronabinol may impair male and female fertility based on animal studies; reversible upon discontinuation. Human data limited. |